Signal transduction by interferon-. alpha. through arachidonic acid metabolism

Journal Article · Fri Jan 11 00:00:00 EST 1991 · Science (Washington, D.C.); (United States)

DOI:https://doi.org/10.1126/science.1898993· OSTI ID:5702464

Hannigan, G E; Williams, B R.G. ^[1]

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1. Univ. of Toronto, Ontario (Canada)

Molecular mechanisms that mediate signal transduction by growth inhibitory cytokines are poorly understood. Type 1 ({alpha} and {beta}) interferons (IFNs) are potent growth inhibitory cytokines whose biological activities depend on induced changes in gene expression. IFN-{alpha} induced the transient activation of phospholipase A{sub 2} in 3T3 fibroblasts and rapid hydrolysis of ({sup 3}H)arachidonic acid (AA) from prelabeled phospholipid pools. The phospholipase inhibitor, bromophenacyl bromide (BPB), specifically blocked IFN-induced binding of nuclear factors to a conserved, IFN-regulated enhancer element, the interferon-stimulated response element (ISRE). BPB also caused a dose-dependent inhibition of IFN-{alpha}-induced ISRE-dependent transcription in transient transfection assays. Specific inhibition of AA oxygenation by eicosatetraynoic acid prevented IFN-{alpha} induction of factor binding to the ISRE. Treatment of intact cells with inhibitors of fatty acid cyclooxygenase or lipoxygenase enzymes resulted in amplification of IFN-{alpha}-induced ISRE binding and gene expression. Thus, IFN-{alpha} receptor-coupled AA hydrolysis may function in activation of latent transcription factors by IFN-{alpha} and provides a system for studying the role of AA metabolism in transduction of growth inhibitory signals.

• OSTI ID: 5702464
• Journal Information: Science (Washington, D.C.); (United States), Vol. 251:4990; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ARACHIDONIC ACID
METABOLISM
INTERFERON
BIOCHEMICAL REACTION KINETICS
LIPASES
ENZYME ACTIVITY
BIOLOGICAL PATHWAYS
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
GENE AMPLIFICATION
GENE REGULATION
INHIBITION
TRACER TECHNIQUES
TRANSCRIPTION FACTORS
TRITIUM COMPOUNDS
CARBOXYLESTERASES
CARBOXYLIC ACIDS
ENZYMES
ESTERASES
GROWTH FACTORS
HYDROGEN COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
KINETICS
LYMPHOKINES
MITOGENS
MONOCARBOXYLIC ACIDS
NUCLEOPROTEINS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
REACTION KINETICS
550201* - Biochemistry- Tracer Techniques